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Cerebrospinal fluid (CSF) findings include lymphocytic pleocytosis of less than 500 white blood cells/mm3 in the majority of POW virus encephalitis cases; granulocytes can predominate early in the disease. CSF protein is generally normal or mildly elevated, while glucose concentration is normal. Electroencephalography (EEG) in patients with POW virus encephalitis reveals generalized slow wave activity and results can resemble those seen in herpes simplex virus encephalitis. MRI of the brain in patients with POW virus encephalitis shows changes consistent with microvascular ischemia or demyelinating disease in the parietal or temporal lobes; results of brain CT scans have not been particularly useful.

POW virus is difficult to isolate from clinical samples; almost all isolates (and positive PCR results) have come from postmortem brain tissue or CSF. Serologic testing remains the primary method for diagnosing POW virus infection. Combined with a consistent clinical presentation in an endemic area, a diagnosis of acute neuroinvasive POW virus disease can be made by the detection of POW virus-specific IgM antibody in serum or CSF. POW virus IgM tests are not commercially available but can be requested through state health department laboratories and CDC. A positive POW virus IgM test result should be confirmed by neutralizing antibody testing of acute- and convalescent-phase serum specimens at a state public health laboratory or CDC. To submit specimens for testing at CDC, please contact your state health department. All POW virus disease cases should be reported to local public health authorities.